Bristow M R, Ginsburg R, Laser J A, McAuley B J, Minobe W
Br J Pharmacol. 1984 Jun;82(2):309-20. doi: 10.1111/j.1476-5381.1984.tb10765.x.
[3H]-nitrendipine binding data and isolated tissue response for five calcium antagonists were evaluated in rabbit myocardium and aorta. The [3H]-nitrendipine binding site was qualitatively identical in myocardium and aorta, as the [3H]-nitrendipine KD, KIS for nicardipine and nifedipine and interactions with verapamil, D600 and diltiazem were not different in aortic and cardiac membranes prepared by similar means. In contrast, the inhibition of the Ca2+-induced contractile response in right ventricular myocardium and aortic ring segments indicated a greater than 10,000 fold selectivity of nicardipine for antagonism of vascular responses. This resulted in a different order of potency for calcium antagonist interaction with the [3H]-nitrendipine binding site in cardiac membranes (nicardipine greater than nifedipine greater than D600 greater than verapamil greater than diltiazem) as compared to antagonism of myocardial tissue response (D600 greater than verapamil greater than or equal to nifedipine greater than nicardipine greater than or equal to diltiazem). In heart the difference between the potency of nicardipine in binding experiments and tissue response approached 4 orders of magnitude. We conclude that tissue response selectivity of calcium antagonists is not explained by heterogeneity of [3H]-nitrendipine binding sites.
在兔心肌和主动脉中评估了5种钙拮抗剂的[3H]-尼群地平结合数据和离体组织反应。[3H]-尼群地平结合位点在心肌和主动脉中性质相同，因为通过类似方法制备的主动脉和心脏膜中，[3H]-尼群地平的解离常数（KD）、尼卡地平与硝苯地平的抑制常数（KIS）以及与维拉帕米、D600和地尔硫䓬的相互作用并无差异。相比之下，右心室心肌和主动脉环段中Ca2+诱导的收缩反应的抑制表明，尼卡地平对血管反应的拮抗具有大于10000倍的选择性。这导致钙拮抗剂与心脏膜中[3H]-尼群地平结合位点相互作用的效价顺序（尼卡地平＞硝苯地平＞D600＞维拉帕米＞地尔硫䓬）与心肌组织反应的拮抗效价顺序（D600＞维拉帕米≥硝苯地平＞尼卡地平≥地尔硫䓬）不同。在心脏中，尼卡地平在结合实验和组织反应中的效价差异接近4个数量级。我们得出结论，钙拮抗剂的组织反应选择性不能用[3H]-尼群地平结合位点的异质性来解释。
